Arylation of pyrrole

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

In terms of methodologies for the preparation of A-arylindoles 140, Buchwald reported improved conditions for the palladium-catalyzed coupling of aryl chlorides, bromides, iodides and triflates 138 with a variety of 2-, 7- and polysubstituted indoles 139 utilizing novel electron-rich biaryl(dialkyl)phosphine ligands in combination with Pd2(dba)3 <00OL1403>. Alternatively, Watanabe reports similar A-arylations of pyrrole, indole and carbazoles with aryl bromides and chlorides using Pd(OAc)2/P(f-Bu)3 in xylene at 120°C <00TL481>. 

An alternate approach for the 1-arylation of pyrroles is offered by their copper catalyzed coupling with aryl bromides and iodides, as depicted in 6.68. The process, run in the presence of trans-N,N -dnnethyl-cyclohcxane-diamine, was also efficient in the A-arylation of pyrazole, imidazole, triazoles and indazole, giving a mixture of isomers in the latter case.100... 

The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 83) (81CC254). 

N-Arylation. The development of palladium chemistry now allows relatively easy N-arylations of pyrroles and indoles, using aryl iodides and bromides <1998JA827, 20000L1403>. The combination of Pd(OAc)2 and DPPF catalyzes the formation of N-aryl azoles 45 in the presence of CS2CO3 or /-BuONa with electron-rich, electron-neutral, or electron-poor aryl halides (Scheme 12) <1998JA827>. The system Pd(OAc)2, SIPrnHCl, NaOH [where SIPr= 1,3-bis... 

The conditions developed by Chan and Lam <1998TL2933, 1998TL2941> can also be applied to pyrroles and indoles for N-arylation with arylboronic acids in the presence of cupric acetate and either triethylamine or pyridine at room temperature <1999T12757>. The use of microwave heating makes Ullman N-arylations of pyrroles and indoles a practical proposition <2003TL4217>. 

In 1981, Itahara reported the palladium acetate-mediated direct arylation of pyrroles and indoles with arenes [59], With (sub)stoichiometric Pd(OAc)2 in benzene and acetic acid, arylation of 1-benzoylpyrrole and 1-acetylindole occurred with moderate to excellent conversions, but gave generally low yields of the desired cross-coupling products (Scheme 14). Direct arylation of isoxazole in the presence of stoichiometric amount of Pd(OAc)2 was also reported by Nakamura et al. [60]. 

Scheme 9.39 Rhodium-catalyzed direct arylation of pyrrole (126) with the aryl iodide 40.

Scheme 9.40 Proposed mechanism of rhodium-catalyzed direct arylations of pyrroles.

A -Arylation of pyrroles can be achieved by conversion of 1-lithiopyrroles into the corresponding zinc compounds and then reaction with aryl bromides using palladium(O) catalysis or by direct reaction of the pyrrole with an aryl halide in the presence of base and the palladium catalyst. ... 

The arylation of pyrroles, furans, and thiophenes, which are generally susceptible to electrophiles, may be considered to proceed through an electrophilic mechanism involving the attack of ArPd(II) species, as judged by the usual substitution pattern [128]. However,other mechanisms seem to be capable of participating as in the above aromatic arylation. 

Pyrimidine was used as an effective directing group for the a-arylation of pyrroles in a reaction between pyrroles 62 and silyl coupling partner 63... 

A method for the direct C3 arylation of pyrroles 68 was developed with the goal of achieving the total synthesis of the lamellarin family of natural products 71. This -selective C-H arylation of pyrroles has a broad scope and is amenable to complex molecule synthesis (14JA13226). 

Controlling site selectivity in Pd-catalyzed arylation of pyrroles 12ACR 936. 

Initial studies were carried out by Hartwig et al. [129] using BINAP (1) or DPPF (9) as the ligand for the Pd-catalyzed arylation of pyrrole, indole, and carbazole (Scheme 13.83). 

In 2010, Jafarpour reported a C-H arylation of pyrroles with aryl iodides under catalytic Pd(OH)2/C in triethanolamine. A number of aryl iodides were coupled to unprotected pyrroles in moderate to good yields [64]. 

Seven-membered fused pyrazole moieties can be accessed through a standard palladium-catalyzed intramolecular direct arylation of pyrroles or indoles with iodopyrazoles (eq 168). ... 

An alternate pathway to the arylacetic acid 7 would involve AT-arylation of suitably substituted pyrrole. However, iV-arylation of pyrroles has been difficult to achieve(iO). We were able to form the C- H sp2) bonds efficiently by the N-arylation of electron deficient pyrroles using aryl boronic acids with Cu(OAc)2 as the catalyst 11). 

Rhazinilam (Intramolecular and Intermolecular C-H Arylation of Pyrroles at the C4 Position)... 

In contrast, Gu and coworkers achieved the synthesis of rhazinal by using an intermoiecuiar C-H arylation of pyrroles at the C3 position and subsequent Heck alkylation (Scheme 16.12b) [26]. When iodopyrrole 60 was reacted with aryl iodide 61 in the presence of catalytic PdCl2, PPh3, and excess amounts of norbornene (6 equiv.), a Catellani-type reaction occurred to give intermediate 62. This intermediate then underwent reductive elimination and norbornene release... 

In 2015, Yamaguchi, Itami, Davies, and coworkers accomplished the synthesis of dictyodendrins A and F, pyrrole-carbazole alkaloids, by catalytic C-H functionalization (Scheme 16.15 compare to Section 16.2.1.7) [32]. This synthesis also utilized a rhodium-catalyzed -selective C-H arylation of pyrroles with aryl iodides as the initial reaction. Pyrrole 84 was coupled with aryl iodide 85 in the presence of the same electron-deficient rhodium catalyst to afford... 

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